Minimally invasive treatment of osteoporotic vertebral compression fracture.
The use of percutaneous vertebroplasty (PV) to treat osteoporotic vertebral fractures is increasing. This investigation assesses the efficacy and safety of PV for refractory pain owing to osteoporotic vertebral compression fractures. A retrospective investigation of PV was conducted with a minimal of 1 year follow up. PV with polymethylmethacrylate (PMMA) was performed on 75 patients with osteoporotic vertebral compression fractures that responded poorly to the conservative therapy. Patients were asked to quantify their degree of pain using Huskisson's visual analogue scale to assess the clinical results. Eighty-seven vertebrae treated using PV in 70 patients were evaluated with a minimal of 1 year follow up. Pain, as assessed on the VAS, decreased from 80+/-16 mm before PV to 36+/-28 mm at 1 month after PV and 30+/-19 mm at the most recent follow up. The reduction in pain from the baseline to 1 month (p=0.031) and to final follow up (p=0.023) were both statistically significant. Sixty-two patients (85.5%) quickly returned to their pre-injury activity level and achieved better quality of life. PV is effective in pain reduction for painful vertebral compression fractures. It provided significant pain relief. Skillful techniques and careful safeguards can minimize the risks of PMMA migration.


Serum-induced demyelination: an electrophysiological and histological study.
Serum from rabbits with EAN in the acute phase of the disease has been injected into rat sciatic nerve, and compared to control rabbit serum and serum from patients with demyelinating neuropathy and to normal human control serum. Electrophysiological studies were performed on all rat sciatic nerves so injected, and the nerve was then removed and examined histologically. Control rabbit and human serum and neuropathic human serum, when injected in a 20 microL quantity through a 30 gauge needle, did not produce significant electrophysiological abnormalities. EAN serum, however, produced significant dispersion of the muscle action potential and conduction block. All serum produced some histological evidence of demyelination but that seen with EAN serum was quite profound compared to all other sera. It is concluded that humoral factors are present within animals with EAN which has potent demyelinating potential. We were not able to demonstrate the same effect from patients with demyelinating neuropathy in this test system.


Dispersion management of a nonlinear amplifying loop mirror-based erbium-doped fiber laser.
We report an investigation of dispersion management of an all-polarization-maintaining Er-fiber oscillator mode-locked via a nonlinear amplification loop mirror in a figure-nine cavity configuration with two output ports. The performance of the laser was investigated within the net cavity dispersion ranging from -0.034 ps2 to +0.006 ps2. We show that the spectral and temporal phase of the pulses at both figure-nine outputs have clearly different characteristics. One of the laser outputs provides pulses with significantly better quality; nonetheless, the rejection output also offers ultrashort pulses with broad spectra. Pulses as short as 79 fs with an energy of 83 pJ were generated directly from the laser in the near-zero dispersion regime.


Reduction of the observed prevalence of so-called non-A non-B hepatitis using sensitive markers of HBV and herpes viruses infections.
In the absence of a specific marker, the observed prevalence of so called non-A non-B hepatitis depends on the sensitivity of the markers of the other viral infections known to induce hepatitis. We have reevaluated this prevalence after using sensitive markers of HBV (HBs monoclonal radioimmunoassay M-RIA and IgM anti-HBc), EBV (IgM anti-VCA), CMV (IgM anti-CMV) and HSV (IgM anti-HSV) in a group of 53 subjects usually considered as having acute or chronic hepatitis. Detection of IgM against HBc, CMV and HSV used immunocapture tests. Among the 37 patients with acute hepatitis, 11 (30 p. 100) were positive for at least one sensitive marker, including 10 markers of HBV (7 M-RIA and 3 IgM anti-HBc) and one IgM anti-CMV. Among the 16 patients with chronic hepatitis, one was positive for HBV by M-RIA; five patients had a false positive reaction to EBV (IgM anti-VCA) disappearing when rheumatoid factor was eliminated. This study shows that many cases of the so-called non-A non-B hepatitis are in fact due to HBV or to a variant of HBV. Definition of non-A non-B hepatitis must include subjects negative for HBV by M-RIA and IgM anti-HBc and negative for CMV by IgM anti-CMV.


The distribution of specific phage types of Salmonella typhimurium in chickens in Australia.
The distribution of specific phage types of Salmonella typhimurium within the Australian chicken industry has been studied and documented on an Australia-wide and state-by-state basis. A total of 1799 strains of S. typhimurium were obtained from Australia-wide sources and phage typing categorized 1498 of these isolates into 30 distinct phage types, with the remaining 301 strains untypable. Five phage types, 6, 26, 31, 135 and 179, accounted for 76% of the total strains typed, with the remaining 24% of strains being distributed among 25 phage types. Of the major phage types, type 31 was restricted to Victoria and Western Australia, but the other types were distributed throughout Australia. In addition, the antibiotic resistance pattern of the various phage types was determined and only five of the 30 phage types showed appreciable levels of resistance.


Responses of trigeminal ganglion neurons during natural whisking behaviors in the awake rat.
Rats use their whiskers to locate and discriminate tactile features of their environment. Mechanoreceptors surrounding each whisker encode and transmit sensory information from the environment to the brain via afferents whose cell bodies lie in the trigeminal ganglion (Vg). These afferents are classified as rapidly (RA) or slowly (SA) adapting by their response to stimulation. The activity of these cells in the awake behaving rat is yet unknown. Therefore, we developed a method to chronically record Vg neurons during natural whisking behaviors and found that all cells exhibited (1) no neuronal activity when the whiskers were not in motion, (2) increased activity when the rat whisked, with activity correlated to whisk frequency, and (3) robust increases in activity when the whiskers contacted an object. Moreover, we observed distinct differences in the firing rates between RA and SA cells, suggesting that they encode distinct aspects of stimuli in the awake rat.


Mutant desmocollin-2 causes arrhythmogenic right ventricular cardiomyopathy.
Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a genetically heterogeneous heart-muscle disorder characterized by progressive fibrofatty replacement of right ventricular myocardium and an increased risk of sudden cardiac death. Mutations in desmosomal proteins that cause ARVC have been previously described; therefore, we investigated 88 unrelated patients with the disorder for mutations in human desmosomal cadherin desmocollin-2 (DSC2). We identified a heterozygous splice-acceptor-site mutation in intron 5 (c.631-2A-->G) of the DSC2 gene, which led to the use of a cryptic splice-acceptor site and the creation of a downstream premature termination codon. Quantitative analysis of cardiac DSC2 expression in patient specimens revealed a marked reduction in the abundance of the mutant transcript. Morpholino knockdown in zebrafish embryos revealed a requirement for dsc2 in the establishment of the normal myocardial structure and function, with reduced desmosomal plaque area, loss of the desmosome extracellular electron-dense midlines, and associated myocardial contractility defects. These data identify DSC2 mutations as a cause of ARVC in humans and demonstrate that physiologic levels of DSC2 are crucial for normal cardiac desmosome formation, early cardiac morphogenesis, and cardiac function.


[Impacts of ODF2 gene knockdown on the sperm motility and fertility of male mice].
To investigate the knockdown of the outer dense fiber protein 2 (ODF2) gene on the sperm motility and fertility of male mice. We constructed three knockdown vectors with the target gene ODF2 and one control vector without the target gene. After infecting ICR mice, we determined the vector with the best knockdown effect by RT-PCR and Western blot and reinfected the mice with it. Then we obtained and analyzed the sperm motility parameters, pathological changes of the testis issue, and the litter size of the mice with gene knockdown. Compared with the normal controls, the mice infected with the vector with the best knockdown effect showed significantly decreased sperm motility parameters, pathomorphological abnormalities of the testis, and a reduced litter size (10.86 ± 1.28 vs 12.72 ± 2.05, P = 0.001). Decreased expression of the ODF2 gene deceases sperm motility parameters, impairs the morphology of the testis and affects the fertility of male mice.


A randomized trial comparing vaginal laser therapy and pelvic floor physical therapy for treating women with stress urinary incontinence.
Female stress urinary incontinence (SUI) is considered a major public health issue. Physical therapy is an important conservative treatment; however, it is primarily limited by poor long-term compliance. Furthermore, surgical treatment entails significant risks. Therefore, new treatment techniques must be identified. To compare the use of laser therapy and pelvic floor (PF) physical therapy for treating postmenopausal women with SUI. This pilot study enrolled 40 women with a clinical and urodynamic diagnosis of SUI who were randomized into two groups: those who received erbium-doped yttrium-aluminum-garnet (Er:YAG) laser therapy implemented over three sessions with a 1-month interval (n = 20) and those who received physical therapy with supervision twice a week for 3 months (n = 20). In total, 16 women completed the treatment in each group. The patients were assessed for PF function using the modified Oxford scale and for pelvic organ prolapse using the Pelvic Organ Prolapse Quantification System. The 1-h pad test and quality of life questionnaires, King's Health Questionnaire (KHQ), and Incontinence Quality of Life (IQOL) were also administered. Patients were re-evaluated at 1, 3, 6, and 12 months after treatment. The mean patient age was 62.7 ± 9.1 and 57.9 ± 6.1 years, median Oxford score at baseline was 3 (2-4.5) and 4 (3-4), mean IQOL score was 79.8 ± 17 and 74.6 ± 18 for physical therapy group (PTG) and laser group (LG), respectively. For the amount of urine leak in the 1-h pad test evaluation, we found significance for the interaction of group and time points only for the Laser intragroup. The cure rate, that is, the rate of reaching an insignificant score in the pad test, at 6 and 12 months was 43.75% and 50% in PTG and 62.5% and 56.25% in the LG, respectively (p > 0.05). IQOL scores demonstrated considerable improvement in both groups (p > 0.05). Upon comparing the initial and follow-up results, the LG showed an improvement at all consultations, whereas the PTG showed improvements at 1, 3, and 6 months but not at 12 months after treatment. KHQ analysis revealed a considerable improvement in the quality of life (QOL) of patients over time, with no substantial difference between the groups. QOL comparison before and after treatment revealed that the vaginal LG improved more consistently in some domains. Only the PTG showed a significant increase in the mean Oxford score from pretreatment to 1 and 3 months after treatment (p < 0.001 and p = 0.002, respectively). However, no statistically significant difference was observed between the groups. Both treatments are safe and have a positive influence on the impact of UI on patients' QOL. The laser caused a greater reduction in the urinary loss, as measured using the weight of pad test, at 6-month and 12-month after treatment without difference with PTG at the end of the follow-up.


Dendrite-free lithium deposition with self-aligned nanorod structure.
Suppressing lithium (Li) dendrite growth is one of the most critical challenges for the development of Li metal batteries. Here, we report for the first time the growth of dendrite-free lithium films with a self-aligned and highly compacted nanorod structure when the film was deposited in the electrolyte consisting of 1.0 M LiPF6 in propylene carbonate with 0.05 M CsPF6 as an additive. Evolution of both the surface and the cross-sectional morphologies of the Li films during repeated Li deposition/stripping processes were systematically investigated. It is found that the formation of the compact Li nanorod structure is preceded by a solid electrolyte interphase (SEI) layer formed on the surface of the substrate. Electrochemical analysis indicates that an initial reduction process occurred at ∼ 2.05 V vs Li/Li(+) before Li deposition is responsible for the formation of the initial SEI, while the X-ray photoelectron spectroscopy indicates that the presence of CsPF6 additive can largely enhance the formation of LiF in this initial SEI. Hence, the smooth Li deposition in Cs(+)-containing electrolyte is the result of a synergistic effect of Cs(+) additive and preformed SEI layer. A fundamental understanding on the composition, internal structure, and evolution of Li metal films may lead to new approaches to stabilize the long-term cycling stability of Li metal and other metal anodes for energy storage applications.


How useful is population data for informing visual field progression rate estimation?
Bayesian estimators allow the frequency of visual field progression rates in the population (the prior distribution) to constrain rate estimates for individuals. We examined the benefits of a prior distribution accounting for one of progression's major risk factors--whether intraocular pressure is treated--to gauge the maximum benefit expected from developing priors for other glaucoma risk factors. Our prior distribution was derived from published data from either treated (matched-prior condition) or untreated (unmatched-prior condition) glaucoma patients. We simulated MD values (6-monthly) with true underlying progression rates drawn from the same distribution as the prior for the matched-prior condition. We estimated rates through linear regression, and determined the likelihood of obtaining this estimate as a function of a range of true underlying progression rates (the likelihood function). The maximum likelihood estimate of rate was the most likely value of the posterior distribution (the product of the prior distribution and likelihood function). For short (4) visual field series, the matched-prior condition, unmatched-prior condition, and linear regression gave median errors (estimated minus true rate) of 0.02, 0.20, and 0.00 dB/y, respectively. Positive predictive values for determining rapidly progressing (<-1 dB/y) rates were 0.46, 0.42, and 0.38, with negative predictive values of 0.93, 0.94, and 0.95. For more extended series the magnitude of the differences between techniques decreased, although the order was unchanged. Performance shifts in bayesian estimators of visual field progression are modest even when prior distributions do not reflect large risk factors, such as IOP treatment.


Brief advice to tuberculosis patients in Nepal to stop smoking: a pilot study by the Britain Nepal Medical Trust.
Tuberculosis (TB) treatment centres in Eastern Nepal. To determine smoking cessation rates among TB patients advised to quit. One intervention and one control centre were studied. At the intervention centre, brief advice about smoking and cessation was given at the start of anti-tuberculosis treatment, and repeated 2 and 5 months later. After 6 months of standard treatment, patients were asked about quitting. Expired air carbon monoxide (CO) was measured in those claiming 6 months of abstinence. None of the 51 controls achieved 6 months of abstinence, whereas 77 (39%) of the 195 in the intervention group claimed at least 6 months of abstinence. All claims were verified by CO measurement in expired air (95%CI 31.4-47.6, P < 0.0001 for the difference in smoking cessation). Brief advice on smoking cessation to patients starting anti-tuberculosis treatment in the National Tuberculosis Programme (NTP) setting in Eastern Nepal led to 39% quitting for least 6 months. Our results should encourage randomised trials in smokers with TB in Nepal: if substantiated, smoking cessation advice should become a mandatory component of the NTP.


Tamoxifen in trimodal therapy with cytotoxic drugs and hyperthermia in vivo significantly enhance therapeutic efficacy against B16-F10 melanoma.
The aim of the study was to investigate whether use of the antiestrogen tamoxifen and heat treatment in combined therapy with the well-known anticancer drugs cisplatin, dacarbazine and cyclophosphamide enhances their therapeutic efficacy on mouse B16-F10 melanoma in vivo. The results of systemic melanoma therapy have been mostly disappointing. Therefore, there is still a great need for strategies that can improve existing chemotherapy options. The tumor model for the investigation of antitumor activity was a mouse B16-F10 melanoma transplanted into the footpad of C57BL/6 Zgr/Hr mice. Drugs were given intraperitoneally 15 min before the application of local hyperthermia, and tumor growth and mouse survival were followed. Hyperthermia alone determined a significant delay of tumor growth, but mouse survival was not affected. In bimodal combinations with hyperthermia, all the tested antitumor drugs significantly increased both tumor growth delay and mouse survival. Tamoxifen alone did not show any inhibitory effect on B16-F10 melanoma in vivo. However, in the trimodal therapy with a particular drug and hyperthermia, it potentiated the inhibitory effects of the respective bimodal treatments, especially that of cyclophosphamide and hyperthermia. Our results obtained on the mouse B16-F10 melanoma in vivo confirmed the enhanced therapeutic efficacy of the trimodal therapy tamoxifen, hyperthermia and anticancer drug combinations in melanoma treatment. Further studies should optimize the heat-drug time scheduling and drug doses that will result in the best possible therapeutic achievement for these trimodal therapy options.


[Nomarski interference microscopy: use of combined contrast uranyl acetate-PTA for in vitro observation of monolayer cultures].
In this paper is reported a technique for the fixation and staining of cellular monolayers in vitro for observation by the interferential microscope according to Nomarski. This method includes the use of glutaraldehyde at 2.5% in phosphate buffer 0.1 M pH 7.5 and the sequential use of Uranil acetate (0.9% in absolute alcohol) and phosphtungstic acid (1% in absolute alcohol). This study has been conducted on 3 cellular lines: PC12 (rat pheocromocytoma), R.P.C. (rat pineal cells), primary culture obtained from a human carcinoma of the uterus.


Isolation of a cDNA and characterization of the 5' flanking region of the gene encoding the type I regulatory subunit of the cAMP-dependent protein kinase.
A bovine cDNA probe for the type I regulatory subunit of the cAMP-dependent protein kinase [Lee et al. (1983) Proc. Natl Acad. Sci. USA 80, 3608-3612] was used to screen two lambda gt11 libraries constructed from poly(A)-rich RNA from the porcine kidney cell line, LLC-PK1. A series of overlapping clones were isolated and characterized. The largest clone, lambda RI15, of 1426 bp was found to code for the entire RI protein but was apparently missing the 3' end of the mRNA. The porcine cDNA codes for a protein of 389 amino acids that shows 99% homology to bovine RI and hybridizes to two major mRNA transcripts of approximately 2.0 kb and 4.5 kb from LLC-PK1 cells. The porcine cDNA for RI was used to screen a genomic library of LLC-PK1 DNA constructed in the EMBL-3 vector and several clones were isolated and characterized. By using a probe from the 5' end of the RI cDNA we isolated the 5' end of the gene and 700 bp of the promoter region of the gene were sequenced. The promoter region lacks a characteristic TATA box but contains two inverted CAAT boxes and is rich in G + C residues. Several sequence motifs were identified in the 5' promoter region which could be responsible for the regulation of synthesis of this gene. Multiple transcription initiation sites were identified by S1 nuclease mapping.


Properties of poly(3-halidethiophene)s.
The influence of the halogen atom on the intrinsic properties of poly(3-halidethiophene)s has been investigated using experimental and theoretical methodologies. Specifically, the electrochemical, electrical, electronic and morphological properties of poly(3-bromothiophene) have been determined and compared with those recently reported for poly(3-chlorothiophene) [Aradilla et al., Polym. Chem., 2012, 3, 436.]. The electrochemical stability and porosity are smaller for poly(3-bromothiophene) than for poly(3-chlorothiophene) while the π-π* lowest transition energy is higher for the former than for the latter. Moreover, quantum mechanical calculations on model oligomers have evidenced that the conformational properties of poly(3-halidethiophene)s, where the halogen is fluorine, chloride or bromine, are dominated by steric interactions and, therefore, are significantly influenced by the size of the halogen atoms. Both the ionization potential and the π-π* lowest transition energy have been predicted to increase slightly when the π-donor character of the halogen atom decreases, in agreement with experimental observations.


Race, violence, and psychopathology.
The frequency of violent behavior among inpatients on an acute psychiatric unit for veterans was examined. Violent behavior was assessed using a modified Lion scale in 93 white and 24 black consecutively admitted inpatients receiving a fixed dose of neuroleptic. Blacks were significantly less violent according to the Lion scale. Item analysis revealed that whites made more violent threats, committed more violent acts against self, and were more likely to be secluded or restrained. Blacks were less likely to commit multiple acts against others, although the actual numbers of violent episodes were not significantly different. No racial differences were seen in serum neuroleptic level, psychopathology as measured by the BPRS, or admission status. The same racial differences in violence were seen when either schizophrenics alone or paranoid schizophrenics were considered.


Long-Term Multifunctional Outcome and Risks of Face Vascularized Composite Allotransplantation.
Vascularized composite allotransplantation (VCA) to reconstruct complex centrally located facial defects and to restore vital functions in a 1-staged procedure has worldwide gained acceptance. Continuous long-term multidisciplinary follow-up of face transplant patients is mandatory for surveillance of the complications associated with the immunosuppressive regime and for functional assessment of the graft. In December 2011, our multidisciplinary team performed a digitally planned face transplant at the Ghent University Hospital, Belgium on a 55-year-old man with a large central facial defect after a high-energy ballistic injury. The patient was closely followed to assess functional recovery, immunosuppressive complications, overall well-being, and quality of life. Three years postoperatively, the patient and his family are very satisfied with the overall outcome, and social reintegration in the community is successful. Motor and sensory functions have recovered near normal. Infectious and medical complications have been serious but successfully managed. Immunosuppressive maintenance therapy consists of corticoids, tacrolimus, and mycophenolate mofetil in minimal doses. Epithetic reconstruction of both eyes gave a tremendous improvement on the overall aesthetic outcome. Despite serious complications during the first 12 months, multifunctional outcome in the first face transplant in Belgium (#19 worldwide) is successful. This should be attributed to the continuous and long-term multidisciplinary team approach. As only few reports of other face transplant patients on long-term follow-up are available, more data need to be collected and reported to further outweigh the risk benefit ratio of this life changing surgery.


Accuracy/diversity and ensemble MLP classifier design.
The difficulties of tuning parameters of multilayer perceptrons (MLP) classifiers are well known. In this paper, a measure is described that is capable of predicting the number of classifier training epochs for achieving optimal performance in an ensemble of MLP classifiers. The measure is computed between pairs of patterns on the training data and is based on a spectral representation of a Boolean function. This representation characterizes the mapping from classifier decisions to target label and allows accuracy and diversity to be incorporated within a single measure. Results on many benchmark problems, including the Olivetti Research Laboratory (ORL) face database demonstrate that the measure is well correlated with base-classifier test error, and may be used to predict the optimal number of training epochs. While correlation with ensemble test error is not quite as strong, it is shown in this paper that the measure may be used to predict number of epochs for optimal ensemble performance. Although the technique is only applicable to two-class problems, it is extended here to multiclass through output coding. For the output-coding technique, a random code matrix is shown to give better performance than one-per-class code, even when the base classifier is well-tuned.


Virtual Travel Training for Autism Spectrum Disorder: Proof-of-Concept Interventional Study.
Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder characterized by impairments in social interaction and repetitive patterns of behavior, which can lead to deficits in adaptive behavior. In this study, a serious game was developed to train individuals with ASD for an important type of outdoor activity, which is the use of buses as a means of transportation. The aim of this study was to develop a serious game that defines a "safe environment" where the players became familiar with the process of taking a bus and to validate if it could be used effectively to teach bus-taking routines and adaptive procedures to individuals with ASD. In the game, players were placed in a three-dimensional city and were submitted to a set of tasks that involved taking buses to reach specific destinations. Participants with ASD (n=10) underwent between 1 to 3 training sessions. Participants with typical development (n=10) were also included in this study for comparison purposes and received 1 control session. We found a statistically significant increase in the measures of knowledge of the process of riding a bus, a reduction in the electrodermal activity (a metric of anxiety) measured inside the bus environments, and a high success rate of their application within the game (93.8%). The developed game proved to be potentially useful in the context of emerging immersive virtual reality technologies, of which use in therapies and serious games is still in its infancy. Our findings suggest that serious games, using these technologies, can be used effectively in helping people with ASD become more independent in outdoor activities, specifically regarding the use of buses for transportation.


Spring nitrate flux in the Mississippi River Basin: a landscape model with conservation applications.
Nitrogen derived from fertilizer runoff in the Mississippi River Basin (MRB) is acknowledged as a primary cause of hypoxia in the Gulf of Mexico. To identify the location and magnitude of nitrate runoff hotspots, and thus determine where increased conservation efforts may best improve water quality, we modeled the relationship between nitrogen inputs and spring nitrate loading in watersheds of the MRB. Fertilizer runoff was found to account for 59% of loading, atmospheric nitrate deposition for 17%, animal waste for 13%, and municipal waste for 11%. A nonlinear relationship between nitrate flux and fertilizer N inputs leads the model to identify a small but intensively cropped portion of the MRB as responsible for most agricultural nitrate runoff. Watersheds of the MRB with the highest rates of fertilizer runoff had the lowest amount of land enrolled in federal conservation programs. Our analysis suggests that scaling conservation effort in proportion to fertilizer use intensity could reduce agricultural nitrogen inputs to the Gulf of Mexico, and that the cost of doing so would be well within historic levels of federal funding for agriculture.


Clinical utility of a genetic susceptibility test for severe chronic periodontitis: a critical evaluation.
A genetic susceptibility test for severe chronic periodontitis is now commercially available. It detects the simultaneous presence of a specific form of two interleukin genes--allele 2 at the IL1A+4845 and IL1B+3954 loci. Patients are referred to as being "genotype-positive" if both of these alleles are present. A fundamental premise of the test is that a combination of these alleles is responsible for increased secretion of IL-beta, which results in a hyperinflammatory response to a bacterial challenge, thereby predisposing a person to develop severe chronic periodontitis. The authors reviewed controlled clinical trials that assessed the association between specific genotypes and the patient's susceptibility to increased bleeding on probing, periodontitis and loss of teeth or dental implants. The relationship between specific IL-1 genotypes and the level of IL-1beta in the gingival crevicular fluid is unclear. Similarly, the ability of the genetic susceptibility test to forecast which patients will develop increased bleeding on probing, periodontitis, or loss of teeth or dental implants is ambiguous. Additional prospective clinical trials are needed to determine the risk of developing periodontitis or peri-implantitis when allele 2 at the IL1A+4845 and IL1B+3954 loci is present. Therefore, it is unclear how results of the genetic susceptibility test can be used to alter patients' periodontal maintenance schedules or to change treatment regimens in periodontally symptomatic or asymptomatic patients.


Self-reported changes in dietary calcium and energy intake predict weight regain following a weight loss diet in obese women.
This study examined relationships between changes in dietary calcium intake, energy intake, and body weight following a weight loss diet. One hundred three overweight or obese women lost weight over 22 wk. Dietary calcium and energy intake were assessed using the Block 98 FFQ (Block) and 5-d food records (FR) at intervention end and 6- and 18-mo follow-up. Pearson correlations were used to relate changes in dietary calcium to energy intake. We used regression analyses to examine relationships between changes in dietary calcium, energy intake, and weight regain. Changes in dietary calcium and energy intake were correlated (r = 0.32; P = 0.033), but neither variable alone predicted weight regain. From 6- to 18-mo follow-up, greater dietary calcium intake inversely predicted weight regain when controlling for changes in energy intake (P = 0.048 Block and 0.025 FR), whereas higher energy intake positively predicted weight regain when controlling for changes in dietary calcium intake (P = 0.009 Block and 0.049 FR) (combined R(2) = 0.153 Block and 0.178 FR). Dietary calcium may oppose weight regain, reducing the effect of greater energy intake. Our results encourage future research on the potential relationship between dietary calcium and weight loss maintenance and suggest that controlling for dietary calcium may increase the ability of energy intake to predict weight change.


Sensitivity of histology for the detection of the amphibian chytrid fungus Batrachochytrium dendrobatidis.
Histology is often underappreciated for the detection of the amphibian pathogenic fungus Batrachochytrium dendrobatidis, the cause of the potentially lethal skin disease chytridiomycosis. We evaluated the sensitivity of histology to detect chytrids in 20 wild specimens of 2 frog species from Uruguay that were clinically normal, but confirmed by PCR to be infected by B. dendrobatidis. We detected maturing and sporulated sporangia in 15 of 20 (75%) frogs, which is more sensitive than previously reported for histology. The effort needed to identify chytrids in histologic skin sections of Physalaemus henselii and Pleurodema bibroni required examination of 3.2 and 8.7 mm of skin sections for each frog species, respectively.


The quinternary chromatin-DNA structure. Three-dimensional reconstruction and functional significance.
Nuclear DNA-space images from Feulgen-stained HeLa cells synchronized at 1, 3, 5, 8, 12, 15, and 18 h following mitosis are digitized and their densitometric-geometric patterns are analyzed by means of a Quantimet 720-D image analyzer on line with a PDP11/40 computer. Frequency distributions of picture point optical densities for the phases and subphases as seen in nuclear images show that DNA packing changes are evident by means of ordinary optical microscopy. Radii of gyration of the images, and optical density profiles and distributions for several squashes of similar cells reveal that in particular instances chromatin DNA is distributed mostly towards the periphery, and usually with high circular isotropy. Cross power spectra of individual scan lines suggest that existence of higher order "quinternary" periodic structure for chromatin that modulates during the cell cycle. Three-dimensional reconstruction 2- micrometer sections of intact, Feulgen-stained mammalian tumor tissue show stainable material only toward the nuclear perimeter and not in the center (compatible with the evidence that initial thymidine incorporation in HeLa cells is generally at the nuclear border). Densitometric properties of reconstructed interphase chromatin-DNA bodies are highly coupled with similar properties of the whole nucleus, showing that a more condensed nucleus is always accompanied by a more condensed interphase chromatin DNA. The effect of micrococcal nuclease digestion on the digitized nuclear images is also presented. All the above data are then discussed in terms of a quinternary chromatin-DNA structure and its modulation during the cell cycle.


A case of neurosarcoidosis that presented with symptoms of Guillain-Barré syndrome.
This case report is of a patient who presented with clinical features suggestive of Guillain-Barré syndrome, who on investigation was found to have neurosarcoidosis. The patient was treated with high-dose corticosteroids and physiotherapy and he improved in condition substantially over 1 month. Neurosarcoidosis and its various presentations are discussed in the literature review.


Knowledge of hepatitis C and treatment willingness amongst people who inject drugs in an era of direct acting antivirals.
Knowledge of hepatitis C virus (HCV) is believed to be important in altering risk behaviour, improving engagement in care, and promoting willingness to initiate HCV treatment. We assessed factors associated with HCV knowledge and treatment willingness amongst people who inject drugs (PWID) in an era of direct acting antivirals. Data were derived from three prospective cohort studies of PWID in Vancouver, Canada, between June 2014 and May 2015. HCV knowledge and treatment willingness were assessed using a Likert scale. Multivariable linear regression identified factors associated with higher HCV knowledge and treatment willingness. Amongst 630 participants, mean scores for HCV knowledge and treatment willingness were 25.41 (standard deviation [SD]: 2.52) out of 30, and 6.83 (SD: 1.83) out of 10, respectively. In multivariable analyses, Caucasian ancestry (adjusted linear regression model estimate [β] 0.50; 95% confidence interval [CI] 0.17, 0.82), employment (β 0.76; 95% CI: 0.38, 1.13), diagnosed mental health disorder (β 0.44; 95% CI: 0.11, 0.78) and previous HCV treatment (β 0.94; 95% CI: 0.46, 1.43) were independently associated with higher knowledge. Downtown Eastside (DTES) residence (i.e., epicenter of Vancouver's drug scene) was independently associated with lower knowledge (β -0.48; 95% CI: -0.81, -0.15). Greater HCV knowledge (β 0.12; 95% CI: 0.07, 0.17) was independently associated with higher HCV treatment willingness. DTES residence (β -0.31; 95% CI: -0.56, -0.06) and daily crack cocaine smoking (β -0.52; 95% CI: -0.92, -0.13) were independently associated with lower treatment willingness. Socioeconomic factors, such as neighborhood residence and employment, were associated with HCV knowledge. Higher HCV knowledge was associated with more HCV treatment willingness. Our findings suggest that increasing HCV knowledge amongst PWID may be an integral component of the HCV cascade of care and that efforts might be best targeted to individuals with greater socioeconomic disadvantage.


The role of class II major histocompatibility complex antigens in autoimmune diabetes: animal models.
Like human insulin-dependent diabetes, autoimmune diabetes in BB rats and NOD mice is under control of Class II genes of the major histocompatibility complex. The mechanisms of expression of these genes is still unclear. No aberrant expression of Class II antigens was found in BB rats at the onset of diabetes. The putative role of inadequate Class II-linked suppressor control is suggested, however, by the observation that in vivo treatment with anti-Class II monoclonal antibody prevents the onset of diabetes in NOD mice, and that this protection can be transfer by CD4+ T cells.


Association of purinergic receptor P2RX7 gene polymorphisms with depression symptoms.
The activation of the ATP-gated P2RX7 (purinergic receptor P2X, ligand-gated ion channel, 7) produces microglial activation, a process which has been demonstrated in depression, bipolar disorder, and schizophrenia. Emerging data over the last years highlighted the importance of P2X7 cation channel as a potential drug target for these central nervous system disorders. The Gln460Arg (rs2230912) polymorphism of the P2RX7 gene has been widely studied in mood disorders, however the results are still controversial. Therefore, we aimed to investigate the C-terminal region of this gene in major depressive and bipolar disorders (MDD and BD) by studying possibly functional, non-synonymous polymorphisms within a 7 kb long region around the Gln460Arg, including Ala348Thr (rs1718119), Thr357Ser (rs2230911), and Glu496Ala (rs3751143) variants. Since Gln460Arg is located at the 3' end of the P2RX7 gene, we included additional, potentially functional single nucleotide polymorphisms (SNPs) from the 3' untranslated region (UTR), which can be in linkage with Gln460Arg. Based on in silico search, we chose two SNPs in putative microRNA target sites which are located in consecutive positions: rs1653625 and rs1718106. P2RX7 SNPs from the C-terminal region were selected based on previous functional assays, 3' UTR variants were chosen using PolymiRTS and Patrocles databases. The genotyping of the non-synonymous SNPs was carried out by pre-designed TaqMan® kits, while the 3' UTR variants were analyzed by PCR-RFLP method. Case-control analyses were carried out between 315 inpatients with acute major depressive episode (195 MDD, 120 BD) and 406 healthy control subjects. The two subscales of the Hospital Anxiety and Depression Scale (HADS) self-report questionnaire were used for quantitative analyses, including an additional, "at-risk" population of 218 patients with diabetes mellitus. The in vitro reporter gene assays were carried out on HEK and SK-N-FI cells transiently transfected with pMIR vector constructs containing the P2RX7 3' UTR downstream of the luciferase gene. Haplotype analysis indicated a relatively high linkage between the analyzed P2RX7 SNPs. Our case-control study did not yield any association between P2RX7 gene variants and depression. However, dimensional analyses showed significant associations of the HADS depression severity scores with Gln460Arg (rs2230912) and Ala348Thr (rs1718119) in the depressed and diabetic patient groups. In the in vitro experiments, the P2RX7 3' UTR constructs with the lowest predicted binding efficiency to their miRNAs showed the highest expression of the gene. The combination of the depression-associated P2RX7 C-terminal and 3' UTR SNPs contributed to the highest depression severity score in the haplotype analysis. Based on our findings, we propose that a P2RX7 haplotype combination of the Gln460Arg and neighboring SNPs contribute to the observed genetic association with depressive symptoms.


Social workers' and nurses' attitudes toward the health care proxy.
Since health care professionals play a critical role in discussing advance directives with patients, their own attitudes toward these directives are important. This study examined the factors associated with health care professionals' attitudes toward the health care proxy, one form of an advance directive. Social workers (n= 115) and nurses (n= 98) had generally positive attitudes toward the health care proxy. Factors that predicted attitudes included profession and training in end of life. Health care professionals who had prior training in end-of-life planning had more positive attitudes toward the health care proxy than those who did not have training. Implications for education of health care professionals are addressed.


Vestibulospinal findings in two syndromes with spontaneous vertigo attacks.
The influence of vestibular dysfunction upon the vestibulospinal reflex (VSR) in two common peripheral syndromes was investigated by two types of posturographic examination: "static" posturography, recording and analyzing the postural sway in stance, and "kinetic" posturography, recording the stepping in place test. The influence of the dysfunction was examined outside the attacks, ie, between attacks and not during or immediately after an attack, in patients with Meniere's disease and in others with a sudden vestibular loss syndrome, "neuronitis." However, in both syndromes the influence of the dysfunction was obvious only in some patients; this indicates that central adaptation intervened in the other patients. In this way, central compensation related to the VSR was assessed and compared with compensation for the vestibulo-ocular reflex assessed by the rotation tests. Discordance was shown in a number of cases, ie, a number of cases showed compensation for one reflex, but not for the other. Comparison of the results of both posturographic methods also showed discordance. Normal performance in the walking test could not always be correlated with normal performance in the standing test and vice versa.


Heat acclimation and HSP-72 expression in exercising humans.
The purpose of this research was to determine the effect of a 7-day heat acclimation protocol on HSP-72 expression in human skeletal muscle, and to examine the relationships between molecular and physiological markers of heat acclimation. Ten recreationally active male subjects (age = 23.3 +/- 2.81 yrs, VO(2peak) = 3.85 +/- 0.11 L . min (-1)) completed a 7-day heat acclimation protocol consisting of cycling at 75 % of VO(2peak) in a hot environment (39.5 degrees C, 27 % RH). Muscle biopsies were obtained on days 1 (HTT1) and 7 (HTT2) prior to, 6 h post, and 24 h postexercise to measure HSP-72 protein via SDS-PAGE and silver staining. Core rectal temperatures (T(C)), intramuscular temperatures (T(IM)), skin temperatures (T(SK)), heart rate (HR), oxygen uptake (VO(2)), sweat rate (SR), and plasma cortisol were measured. TC, HR, and plasma cortisol were significantly lower in HTT2 than HTT1 (p < or = 0.05). No significant differences were seen for VO(2), TIM, TSK, or SR when comparing HTT2 with HTT1 (p < or = 0.05). No significant time or day x time interactions were detected for HSP-72 expression (24.48 +/- 2.55 vs. 25.04 +/- 1.43 ng/microg protein for HTT1 and HTT2, respectively, p < or = 0.05). Evidence of heat acclimation was seen at the physiological level; however, no evidence of enhanced thermotolerance at the cellular level was indicated by HSP-72 expression.


[Hydrochemical Characteristics and Factors of Surface Water and Groundwater in the Upper Yongding River Basin].
The Yongding River basin is an important water conservation and ecological barrier area in the Northwest of Hebei Province. Reduced runoff and deterioration of the water environment in this area have become increasingly prominent under the effects of climate change and intensive human activities. Clarifying the chemical characteristics and factors of surface water and groundwater in the upper Yongding River basin can provide data and support for the sustainable use of water resources. Stable isotopes of hydrogen and oxygen (δ2H and δ18O) were used to study the sources of surface water and groundwater. Mathematical statistics and hydrogeochemical methods were then used to analyze the regional hydrogeochemical processes and factors of surface water and groundwater. The results showed that precipitation was the main source of surface water and groundwater. Under the effects of natural factors and human activities, the Yang River and Sanggan River basins exhibited significant differences in surface water chemistry. The sub-basins were ranked by ion concentration as follows: Sanggan River>Yang River. The main cation and anions of the Sanggan River basin were Na+, Cl-, and SO42-, while in the Yang River basin, Ca2+ and HCO3- were the most common. The water chemistry of the Sanggan River exhibited greater variation than that of the Yang River. Surface water chemistry were mainly controlled by mineral dissolution and evaporation, but human activities were reflected in different sub-basins. Surface water in the Sanggan River basin was affected by industrial wastewater discharge, while that of the Yang River basin was affected by agricultural production and cities. However, the continuous increase of Cl- and SO42- concentrations, caused by industrial wastewater discharge and acid rain, was the limiting factor for sustainable use of surface water resources. In future, surface water in Sanggan River basin should be used with consideration to the effects of both total salinity and chemical composition of the water, while in Yang River, a focus should be placed on total salinity. The use of surface water resources in accordance with local conditions is an effective measure for the sustainable use of water resources and the restoration of groundwater levels in this region.


How future trends in societal aging, air bag availability, seat belt use, and fleet composition will affect serious injury risk and occurrence in the United States.
The objective of this study was to quantify the importance of societal aging relative to other factors that are known to affect injury risk. An aging population's effect on Maximum Abbreviated Injury Scale (MAIS) 3+ injury trends for passenger car drivers in frontal crashes was projected and compared to the effects of projected changes in fleet composition, changes in seat belt usage, and changes in air bag availability. It was determined that increased frailty due to an aging population will result in 19,816 to 43,568 additional injuries to passenger car drivers in frontal crashes from 1996 to 2012. Aging was shown to have an effect similar to the increased presence of light trucks in the fleet (a cumulative increase of approximately 47,428 injuries). Aging and changing fleet composition were shown to have a smaller effect than the projected increases in seat belt use or air bag availability, though the effect of increased belt use is not much greater than the effect of aging. After 2012, however, air bag availability and seat belt use will plateau, while societal aging will continue.


Normalization of compression-induced hemodynamics in patients responding to neoadjuvant chemotherapy monitored by dynamic tomographic optical breast imaging (DTOBI).
We characterize novel breast cancer imaging biomarkers for monitoring neoadjuvant chemotherapy (NACT) and predicting outcome. Specifically, we recruited 30 patients for a pilot study in which NACT patients were imaged using dynamic tomographic optical breast imaging (DTOBI) to quantify the hemodynamic changes due to partial mammographic compression. DTOBI scans were obtained pre-treatment (referred to as day 0), as well as 7 and 30 days into therapy on female patients undergoing NACT. We present data for the 13 patients who participated in both day 0 and 7 measurements and had evaluable data, of which 7 also returned for day 30 measurements. We acquired optical images over 2 minutes following 4-8 lbs (18-36 N) of compression. The timecourses of tissue-volume averaged total hemoglobin (HbT), as well as hemoglobin oxygen saturation (SO2) in the tumor vs. surrounding tissues were compared. Outcome prediction metrics based on the differential behavior in tumor vs. normal areas for responders (>50% reduction in maximum diameter) vs. non-responders were analyzed for statistical significance. At baseline, all patients exhibit an initial decrease followed by delayed recovery in HbT, and SO2 in the tumor area, in contrast to almost immediate recovery in surrounding tissue. At day 7 and 30, this contrast is maintained in non-responders; however, in responders, the contrast in hemodynamic time-courses between tumor and normal tissue starts decreasing at day 7 and substantially disappears at day 30. At day 30 into NACT, responding tumors demonstrate "normalization" of compression induced hemodynamics vs. surrounding normal tissue whereas non-responding tumors did not. This data suggests that DTOBI imaging biomarkers, which are governed by the interplay between tissue biomechanics and oxygen metabolism, may be suitable for guiding NACT by offering early predictions of treatment outcome.


[Congenital cysts of the larynx].
Based on our own observation of one case of congenital laryngeal cyst of the newborn and a review of 48 cases presented in literature, this congenital anomaly is described. The clinical picture is demonstrated and the genesis of these cysts is discussed.


Risk association between human leukocyte antigen-A allele and high-risk human papillomavirus infection for cervical neoplasia in Chinese women.
To examine the association between human leukocyte antigen-A (HLA-A) allele polymorphism, human papillomavirus (HPV) infection, and risk for cervical neoplasia in Chinese women, 263 patients (155 with cervical intraepithelial neoplasia [CIN] II/III and 108 with invasive cervical cancer [ICC]) were compared with 572 controls. Overall, regardless of HPV status, a decreased risk for ICC was observed for patients with A*0207/0215N or A*2402, and an increased risk was observed for patients with A*1104. The protective association of A*0207/0215N was reproduced in HPV-16-positive patients with ICC, but not in subgroups infected with other HPV types. The risk association between A*1104 and both HPV-16 and HPV-18 was reproduced in the subgroups with CIN III/ICC. The protective association between A*2402 and HPV-16, HPV-18, HPV-52, and HPV-58 was consistently observed in all subgroups with CIN III/ICC, suggesting a linkage with a general antioncogenic genetic factor. The results of the present study indicate that HLA-A polymorphism is one of the host genetic factors that alter the risk for the development of cervical cancer in Chinese women.


If the coping fits, use it: Preadolescent recent stress exposure differentially predicts post-TSST salivary cortisol recovery.
This study examined recent stress exposure and effortful coping effects on salivary cortisol (sC) response patterns in preadolescent boys and girls (N = 121, Mage = 10.60 years). Children were exposed to the Trier Social Stress Test (TSST) and one of two randomly assigned, post-TSST coping conditions: distraction and avoidance. Piecewise growth multilevel modeling did not link children's recent stressful life events or hair cortisol (hC) levels to sC reactivity, though each interacted with coping condition to predict sC recovery patterns. Children with elevated life stressor and hC levels demonstrated protracted sC recovery when primed with distraction, yet more efficient sC recovery when primed with avoidance. Findings challenge assumptions about universally "good" and "bad" coping by highlighting contexts where each succeed and fail in helping children manage acute stress physiology.


Use of routine quality assurance procedures to detect the loss of a linear accelerator primary scattering foil.
The effects of the mechanical loss of a stainless steel primary scattering foil on a 12-MeV electron beam from a dedicated intraoperative electron accelerator are discussed. Routine quality assurance tests, including dose output constancy, energy constancy, and beam uniformity (flatness and symmetry), were used to determine the nature of the malfunction when it occurred. It is concluded that these quality assurance checks, if done with the frequencies recommended by the AAPM Task Group 40 Report [Med. Phys. 21, 581-619 (1994)] and repeated at the time of occurrence, are sufficient to detect loss of an electron scattering foil.


America under attack: the "10 commandments" of responding to mass terrorist attacks.
On September 11, 2001 terrorist attacks caused the catastrophic collapse of the twin towers of the World Trade Center in New York City. Approximately 40 minutes after the World Trade Center was attacked, a similar terrorist attack was perpetrated against the Pentagon in Washington, D.C. Although the resultant physical devastation was beyond anything this nation has ever experienced, the psychological devastation may not be known for months, or even years. This paper discusses, not only a structure for understanding the phases of terrorism, but offers 10 recommendations for responding to acts of terrorism.


Incidence and Risk Factors for Stroke in Fast-Track Hip and Knee Arthroplasty-A Clinical Registry Study of 24,862 Procedures.
Postoperative stroke is a severe complication with a reported 30-day incidence of 0.4%-0.6% after total hip (THA) and knee arthroplasty (TKA). However, most data are based on diagnostic codes and with limited details on perioperative care, including the use of fast-track protocols. We investigated the incidence of and preoperative and postoperative factors for stroke after fast-track THA/TKA. We used an observational study design of elective fast-track THA/TKA patients with prospective collection of comorbidity and complete 90-day follow-up. Medical records were evaluated for events potentially disposing to stroke. Identification of relevant preoperative risk factors was done by multivariable logistic regression. Incidence of stroke was compared with a Danish background population. Of 24,862 procedures with a median length of stay of 2 (interquartile range, 2-3) days, we found 27 (0.11%; 95% confidence interval [CI], 0.08%-0.16%) and 43 strokes (0.17%, 95% CI, 0.13%-0.23%) ≤30 and ≤90 days after surgery, respectively. Preoperative risk factors for stroke ≤30 days were age ≥ 85 years (odds ratio [OR], 4.3; 95% CI, 1.1-16.3) and anticoagulant treatment (OR, 3.1; 95% CI, 1.2-7.9). Preoperative anemia was near significant (OR, 2.1; 95% CI, 0.98-4.6, P = .055). Eight strokes ≤30 days were preceded by a cardiovascular event within the second postoperative day. Incidence of stroke after postoperative day 30 was similar to a Danish background population. Risk of postoperative stroke in fast-track THA and TKA was low but may be further reduced with increased focus on avoiding perioperative cardiovascular events and in patients with preoperative anticoagulants or anemia.


Endosomal acidic pH-induced conformational changes of a cytosol-penetrating antibody mediate endosomal escape.
Endosomal escape after endocytosis is a critical step for protein-based agents to exhibit their effects in the cytosol of cells. However, antibodies internalized into cells by endocytosis cannot reach the cytosol due to their inability to escape from endosomes. Here, we report a unique endosomal escape mechanism of the IgG-format TMab4 antibody, which can reach the cytosol of living cells after internalization. Dissociation of TMab4 from its cell surface receptor heparan sulfate proteoglycan by activated heparanase in acidified early endosomes and then local structural changes of the endosomal escape motif of TMab4 in response to the acidified endosomal pH were critical for the formation of membrane pores through which TMab4 escaped into the cytosol. Identification of structural determinants of endosomal escape led us to generate a TMab4 variant with ~3-fold improved endosomal escape efficiency. Our finding of the endosomal escape mechanism of the cytosol-penetrating antibody and its improvement will establish a platform technology that enables a full-length IgG antibody to directly target cytosolic proteins.


Nuclear genes with sex bias in Ruditapes philippinarum (Bivalvia, veneridae): Mitochondrial inheritance and sex determination in DUI species.
Mitochondria are inherited maternally in most metazoans, but in bivalves with Doubly Uniparental Inheritance (DUI) a mitochondrial lineage is transmitted through eggs (F-type), and another through sperm (M-type). In DUI species, a sex-ratio distortion of the progeny was observed: some females produce a female-biased offspring (female-biased family), others a male-biased progeny (male-biased family), and others a 50:50 sex-ratio. A peculiar segregation pattern of M-type mitochondria in DUI organisms appears to be correlated with the sex bias of these families. According to a proposed model for the inheritance of M-type mitochondria in DUI, the transmission of sperm mitochondria is controlled by three nuclear genes, named W, X, and Z. An additional S gene with different dosage effect would be involved in sex determination. In this study, we analyzed structure and localization of three transcripts (psa, birc, and anubl1) with specific sex and family biases in the Manila clam Ruditapes philippinarum. In situ hybridization confirmed the localization of these transcripts in gametogenic cells. In other animals, homologs of these genes are involved in reproduction and ubiquitination. We hypothesized that these genes may have a role in sex determination and could also be responsible for the maintenance/degradation of spermatozoon mitochondria during embryo development of the DUI species R. philippinarum, so that we propose them as candidate factors of the W/X/Z/S system.


[Estrogenic Activities of Alcohol Extract from Phellinus lonicerinus].
To investigate the estrogenic activities of alcohol extract from Phellinus lonicerinus( AEPL). Estrogen and anti-estrogen effects were evaluated by cell proliferation experiment in vitro. Through elevating young rat uterine weight, castrated female rats, and adult female rats uterus index serum estradiol( E2) and progesterone( P) were analyzed by enzyme immune methods, and uterine estrogen receptor α( ERα) and estrogen receptor β( ERβ) protein expressions were measeured by immunohistochemisty, and investigated the histopathological of uterus, ovary, and breast of adult female rats. Compared with the control group, AEPL promoted estrogen-sensitive MCF-7 proliferation significantly( P < 0. 05 or P < 0. 01) in the doses of 5 ~ 50 μg / m L in vitro experiment; compared with the E2 control group, it also presented anti-estrogenic effect in E2-induced MCF-7 cells at the doses of 10 ~ 100 μg / m L( P < 0. 05 or P < 0. 01). In the animal experiments, AEPL remarkably increased serum E2 content and promoted growth of uterus in primary female mice at the dose of 300 mg / kg; and raised the serum E2 and P content, alleviated uterine atrophy caused by estrogen deficiency in castrated rats at the dose of 240 mg / kg. In adult female rats, AEPL markedly increased the serum P content at the dose of 120 mg / kg, and also markedly increased the serum E2 content at the dose of 120,240 mg / kg, and regulated the protein expressions of ERαand ERβ. AEPL has no effects on histopathological changes of uterus, ovary and mammary gland in rats. AEPL shows estrogenic effects with fewer adverse reaction, which possesses the replacement of estrogen application prospects.


Co-occurrence of a novel PDGFRB variant and likely pathogenic variant in CASR in an individual with extensive intracranial calcifications and hypocalcaemia.
This case report describes an individual with brain calcifications, cognitive decline, motor dysfunction, and hypocalcaemia. Exome sequencing revealed a previously reported variant in the CASR gene and a variant of uncertain significance in PDGFRB. The clinical phenotype is likely explained by the CASR variant, but we discuss how the PDGFRB variant could also participate in the phenotype.


Singular value decomposition filtering for enhanced signal extraction from two-dimensional beam emission spectroscopy measurements.
The signal-to-noise ratio (SNR) of extracted turbulence features from beam emission spectroscopy (BES) data is significantly enhanced via application of singular value decomposition (SVD) methods. BES measures two-dimensional localized density fluctuations in DIII-D. The SNR of core turbulence characteristics is typically limited by noise arising from electronic noise, photon noise, and fluctuations in the observed neutral beam. SVD filtering has led to a significant enhancement in the SNR, reducing errors in time-resolved measurements of core turbulence characteristics, including correlation lengths, decorrelation rates, and group velocities. The SVD filtration technique is applied to BES data by combining multiple physically adjacent sampling locations to extract spatially correlated signals while partially removing unwanted incoherent noise. Using approximately half of the singular value weighted modes to reconstruct turbulence signals is found to improve SNR by up to a factor of 4, while maintaining the spatial structure of the turbulence. Unique aspects of application of SVD to broadband turbulence data are discussed.


Reporting LDL cholesterol results by clinical biochemistry laboratories in Czechia and Slovakia to improve the detection rate of familial hypercholesterolemia.
This survey aims to assess the implementation of recommendations from the European Atherosclerosis Society (EAS) and the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) by clinical biochemistry laboratories in Czechia and Slovakia in their policies for reporting low-density lipoprotein cholesterol (LDL-C) concentrations. The web-based survey was distributed to all 383 Czech and Slovak clinical biochemistry laboratories that measure lipids by external quality assessment provider SEKK. A total of 17 single-answer questions were included. The questionnaire was focused on the detection and decision points in familial hypercholesterolemia (FH). All survey answers were taken into account. The laboratories followed the EFLM and EAS guidelines when they reported an interpretative comment considering FH diagnosis in adults. A total of 203 (53%) laboratories answered. Only 5% of laboratories added interpretative comments considering FH diagnosis when LDL-C concentrations are above 5.0 mmol/L in adults, and 3% of laboratories added interpretative comments considering FH diagnosis when LDL-C concentrations are above 4.0 mmol/L in children. Only 7% of laboratories reported goals for all cardiovascular risk categories (low, moderate, high, very high). Non-HDL cholesterol concentrations were calculated by 74% of responders. A significant number (51%) of participants did not measure apolipoprotein B, and 59% of laboratories did not measure lipoprotein(a). Only a small portion of laboratories from Czechia and Slovakia reported high LDL-C results with interpretative comments considering FH diagnosis in adults, the laboratories did not follow the guidelines.


Growth substrates alter aboveground plant microbial and metabolic properties thereby influencing insect herbivore performance.
The gut microbiome of plant-eaters is affected by the food they eat, but it is currently unclear how the plant metabolome and microbiome are influenced by the substrate the plant grows in and how this subsequently impacts the feeding behavior and gut microbiomes of insect herbivores. Here, we use Plutella xylostella caterpillars and show that the larvae prefer leaves of cabbage plants growing in a vermiculite substrate to those from plants growing in conventional soil systems. From a plant metabolomics analysis, we identified 20 plant metabolites that were related to caterpillar feeding performance. In a bioassay, the effects of these plant metabolites on insects' feeding were tested. Nitrate and compounds enriched with leaves of soilless cultivation promoted the feeding of insects, while compounds enriched with leaves of plants growing in natural soil decreased feeding. Several microbial groups (e.g., Sporolactobacillus, Haliangium) detected inside the plant correlated with caterpillar feeding performance and other microbial groups, such as Ramlibacter and Methylophilus, correlated with the gut microbiome. Our results highlight the role of growth substrates on the food metabolome and microbiome and on the feeding performance and the gut microbiome of plant feeders. It illustrates how belowground factors can influence the aboveground properties of plant-animal systems, which has important implications for plant growth and pest control.


Linear and whorled naevoid hypermelanosis in a patient with trisomy 4 mosaicism.
Linear whorled naevoid hypermelanosis (LWNH) is a rare skin condition, characterized by swirls and whorls of hyperpigmented macules distributed in a reticulate pattern along the lines of Blaschko. We report a 2-year-old boy who presented with linear and whorled hyperpigmentation on his trunk and limbs, following the lines of Blaschko. Hyperkinesia and developmental speech-language impairment were also present. A biopsy specimen showed increased pigmentation within the basal keratinocytes without incontinentia pigmenti. No chromosomal abnormality was found in peripheral blood samples. Chromosomal analysis of skin fibroblasts detected trisomy 4 mosaicism. This case shows for the first time an association of LWNH with trisomy 4 mosaicism. LWNH should not be considered a single entity, but a cutaneous expression of mosaicism.


Liver fibrosis stage predicts early treatment outcomes with peginterferon plus ribavirin in HIV/hepatitis C virus co-infected patients.
Thirty-six HIV-infected patients with chronic hepatitis C treated with peginterferon alpha-2a or 2b plus ribavirin were analysed in a prospective observational study. The were 15 (42%) treatment discontinuations; bt intent-to-treat virological responders were 19 (53%) at week 24. A higher fibrosis score predicted premature discontinuation of hepatitis C virus (HCV) therapy and a lack of early virological response. Female sex and HCV genotype predicted early virological responses. Results support the early treatment of HCV in co-infected individuals.


Defining Essential Services for Deaf and Hard of Hearing Children during the COVID-19 Pandemic.
COVID-19 is a rapidly growing global pandemic caused by a novel coronavirus. With no vaccine or definitive treatment, public health authorities have recommended a strategy of "social distancing," reducing individual interaction, canceling elective procedures, and limiting nonessential services. Health care providers must determine what procedures are considered "elective," balancing risk of treatment delays with that of coronavirus exposure to patient, family, and providers. Given critical periods for language development and the long-term impact of auditory deprivation, some audiologic and otologic services should be considered essential. In this article, we describe the experience of a quaternary referral pediatric hospital in Seattle, the epicenter of COVID-19 in the United States, and share strategies for risk minimization employed by Seattle Children's Hospital. We hope that this work can be a reference for other centers continuing care for children who are deaf and hard of hearing during the COVID-19 and future resource-limiting crises.


[Congenital parotid fistula].
21 cases of congenital parotid fistula are reported. The patients' age ranged from 7 to 50 years. Dissection of the fistula under local anesthesia was made in 9 patients. A 7-year-old patient was operated under intravenous calipsol anesthesia. Four kinds of the fistula depending on its shape and size are described. Two of them cause no trouble, the other two manifest from early childhood with inflammation, recurrences with abscesses. In such cases the fistula should be radically removed.


Successful Combined Treatment of Giant Carotid Body Tumor with Embolization Applied before Surgery.
Carotid body tumors are defined as unusual tumors of neuroectodermal origin that occur in the carotid bifurcation. These generally benign masses grow slowly; then, they become symptomatic with enlargement. In this study, we present a case of a 66-year-old female patient diagnosed with a carotid body tumor with a diameter of 8×9×10 cm. The patient was surgically treated 2 days after embolization due to the wideness of the mass and surgical comorbidity. Furthermore, this article puts emphasis on the importance of embolization before curative surgery in carotid body tumors with large and high blood supply.


Second annual Helene Hudson Memorial Lecture. I am a nurse.
The focus of this study was an exploration of the nature of exceptionally competent oncology nursing practice. Through a combination of data gathering approaches--conversation, observation and narrative exchange--the beliefs, actions and effects of the actions of eight exemplary nurse informants were studied. Analysis revealed three themes related to the action of the exemplary nurses: Dialogue in silence, mutual touch and sharing the lighter side of life. Additional analysis led to a category called effects of nursing actions. Again, three themes were highlighted as effects: Affirmation of the nurse and patient, connecting and joint transcendence.


Synthesis of coumarin derivatives with cytotoxic, antibacterial and antifungal activity.
The synthesis and selective biological screening of 7-hydroxy-4-methyl-2H-chromen-2-one (2), 7-hydroxy-4,5-dimethyl-2H-chromen-2-one (15) and some of their derivatives were carried out. Compound 13 was found to be most potent cytotoxic agent with LD50 = 126.69 microg/ml. In antibacterial assay the compounds showed a broad spectrum of activities. Compound 11 exhibited a very high degree of plant growth inhibition at three levels of concentration. Compound 4 showed very promising antifungal activity against Candida albicans. Compounds 12 and 13 demonstrated excellent antioxidant activity.


Animal Model of Chronic Tympanic Membrane Perforation.
Chronic tympanic membrane perforations (TMP) can be a source of significant morbidity from hearing loss, recurrent middle ear infections, changes in lifestyle, and risk of cholesteatoma formation. Laboratory experiments of TMP have been fraught by the rapid and high rate of spontaneous healing observed in animal models. There is controversy on the minimal time that perforations in animal models must have in order to be considered chronic TMP and thus have clinical relevance, with authors suggesting time periods of perforation patency of 8-12 weeks. In this article, we sought to create a clinically significant experimental model that could yield a high rate of perforation patency for at least 8 weeks. Animals undergoing acute TMP were exposed to three different experimental situations to delay the healing of the perforation: fractionated radiation, topical lipopolysaccharide application, and a combined dexamethasone and mitomycin C (DXM/MC) solution. In our study, the use of DXM/MC reliably produced TMP lasting at least 8 weeks in 86.48% of the cases without the need to reopen the perforation, infolding the edges of the membrane, or using physical barriers to prevent TMP closure. Histologically, the resulting perforated tympanum showed hyaline changes of the remnant tympanum and hyperkeratosis of the squamous epithelia of the external auditory canal. We believe that this model is reproducible and has potential use in experiments of delayed healing of TMP. Anat Rec, 303:619-625, 2020. © 2019 American Association for Anatomy.


[An association between moya-moya disease and morning glory anomaly].
The morning glory disc anomaly is a not very frequent congenital alteration of the optic papilla associated with a retinal vascular dysgenesia. Several cases of association have been described between this disc anomaly and the presence of Moyamoya vessels. We report the case of a boy with this association. A 5 year-old boy was evaluated for several episodes of disconnection, some of them preceded by intense headaches and associated to incoherent language, and in other occasions with hypotonia and unmotivated laugh of variable duration. The physical and neurological exploration was normal, except for the optic disc papilla of the right eye that was very big and dug, compatible with Morning glory disc anomaly. No alterations were found at cranial CT and EEG. In the magnetic resonance imaging were visualized multiple small round low intensity areas in the basal ganglia, because of the high number of collateral vessels. The angioRM showed stenosis of the supraclinoid portions of both internal carotids as well as the proximal segments of the anterior cerebral artery and the left middle cerebral artery with abnormal network of collateral vessels at the base of the brain like a puff of smoke . This is a typical imaging for Moyamoya disease. In all patient with Morning glory disc anomaly, mainly if they presents neurological clinical features, the realization of angioRM studies will be evaluated, to discard the existence of Moyamoya disease.


Enhanced 3-methylcatechol production by Pseudomonas putida TODE1 in a two-phase biotransformation system.
In this study, genetically engineered Pseudomonas putida TODE1 served as a biocatalyst for the bioproduction of valuable 3-methylcatechol (3MC) from toluene in an aqueous-organic two-phase system. The two-phase system was used as an approach to increase the biocatalyst efficiency. Among the organic solvent tested, n-decanol offered several benefits including having the highest partitioning of 3MC, with a high 3MC yield and low cell toxicity. The effect of media supplementation with carbon/energy sources (glucose, glycerol, acetate and succinate), divalent metal cations (Mg(2+), Ca(2+), Mn(2+) and Fe(2+)), and short-chain alcohols (ethanol, n-propanol and n-butanol) as a cofactor regeneration system on the toluene dioxygenase (TDO) activity, cell viability, and overall 3MC yield were evaluated. Along with the two-step cell preparation protocol, supplementation of the medium with 4 mM glycerol as a carbon/energy source, and 0.4 mM Fe(2+) as a cofactor for TDO significantly enhanced the 3MC production level. When in combination with the use of n-decanol and n-butanol as the organic phase, a maximum overall 3MC concentration of 31.8 mM (166 mM in the organic phase) was obtained in a small-scale production, while it was at 160.5 mM (333.2 mM in the organic phase) in a 2-L scale. To our knowledge, this is the highest 3MC yield obtained from a TDO-based system so far.


Side-to-Side Difference of Metatarsal Rotation in Normal Individuals.
A previous study defined the normal first metatarsal pronation angle (MPA) as <16 degrees and normal α angle as <18 degrees. The primary purpose of this study was to assess the side-to-side variation in first metatarsal pronation between feet in normal individuals. MPA and α angles were measured on standardized coronal weightbearing computed tomography slices. Pairedt tests were used to test significance of mean side-to-side differences in a population of 63 normal, asymptomatic individuals. The mean side-to-side difference in first metatarsal pronation was 4.3 degrees (95% CI 3.3, 5.2 degrees) for MPA and 4.9 degrees (95% CI 3.8, 6.0 degrees) for α angle. The normative range for side-to-side difference was calculated as 12 degrees for MPA and 14 degrees for α angle, as defined by 2 SDs from the mean. In a cohort of normal patients, the mean difference in first metatarsal pronation between sides was approximately 4 to 5 degrees based on MPA and α angle. However, considerable variation in differences was observed. These findings may be considered when assessing first metatarsal pronation using population-based values as it may influence thresholds for identifying pathology in an individual.


A Genetic Model to Study Increased Hexosamine Biosynthetic Flux.
Recently, we identified harvest moon (hmn), a fully penetrant and expressive recessive zebrafish mutant with hepatic steatosis. Larvae showed increased triacylglycerol in the absence of other obvious defects. When we attempted to raise these otherwise normal-appearing mutants to adulthood, we observed a developmental arrest and death in the early juvenile period. In this study, we report the positional cloning of the hmn locus and characterization of the defects caused by the mutation. Using bulk segregant analysis and fine mapping, we find that hmn mutants harbor a point mutation in an invariant residue within the sugar isomerase 1 domain of the gene encoding the rate-limiting enzyme of the hexosamine biosynthetic pathway (HBP) glutamine-fructose-6-phosphate transamidase (Gfpt1). The mutated protein shows increased abundance. The HBP generates β-N-acetyl-glucosamine (GlcNAc) as a spillover pathway from glucose. GlcNAc can be O-linked to seryl and threonyl residues of diverse cellular proteins (O-GlcNAc modification). Although some of these O-GlcNAc modifications serve an essential structural role, many others are dynamically generated on signaling molecules, including several impacting insulin signaling. We find that gfpt1 mutants show global increase in O-GlcNAc modification, and, surprisingly, lower fasting blood glucose in males. Taken together with our previously reported work, the gfpt1 mutant we isolated demonstrates that global increase in O-GlcNAc modification causes some severe insulin resistance phenotypes (hepatic steatosis and runting) but does not cause hyperglycemia. This animal model will provide a platform for dissecting how O-GlcNAc modification alters insulin responsiveness in multiple tissues.


The use of two populations of hepatocytes with different triacylglycerol contents as a model to study the accumulation of liver lipid in the laying hen.
(1) A method has been developed to separate hepatocytes, isolated from laying hens, according to their densities, using discontinuous density-gradient centrifugation on Nycodenz. (2) The hepatocytes recovered from the interface of the 5% and 10% Nycodenz layers were rich in triacylglycerol and were termed 'fatty' hepatocytes: 'non-fatty' hepatocytes were obtained from the interface of the 15% and 30% Nycodenz layers and contained less than one-quarter as much triacylglycerol. (3) 'Fatty' hepatocytes incorporated radiolabelled glucose and glycerol into total lipid at more than twice the rate of 'non-fatty' cells: the corresponding increases in the incorporation of radiolabelled choline and valine into phospholipid and protein respectively were smaller and not statistically significant. (4) A higher proportion of glycerol and glucose incorporated into total lipid was found to be phospholipid in the 'non-fatty' hepatocytes. (5) A higher proportion of radiolabelled lipid or protein formed from glycerol or valine respectively was secreted into the medium by the 'non-fatty' hepatocytes. (6) The use of these hepatocytes as a model to study fatty liver syndromes is discussed.


Diastereoselective Synthesis of Monofluorocyclohexenes through Photocatalyzed Cascade Cyclization of gem-Difluoroalkenes and α,β-Unsaturated Carbonyl Compounds.
Monofluoroalkenes are nonhydrolyzable mimetics of amides. Previous work focused on the synthesis of non-cyclic monofluoroalkenes. However, diastereoselective synthesis of monofluorocyclohexenes from non-cyclic substrates is challenging. Herein, we report the first photocatalyzed cascade cyclization reactions of readily available α,β-unsaturated carbonyl compounds and gem-difluoroalkenes for the synthesis of highly functionalized monofluorocyclohexenes. The reaction shows broad substrate scope with high diastereoselectivity (>30 examples, up to 86 % yield, >20 : 1 dr). The post-reaction transformations of the products demonstrate the synthetic potential of this methodology.


[Fluorescence monitoring of solid-phase peptide synthesis using a quartz reactor-cuvette].
The quartz reactor-cuvette for fluorescent monitoring of the solid phase peptide synthesis consists of a 10 mm diameter quartz tube jacketed in a 14 x 14 mm orthogonal holder and equipped with chemically inert adapters. This allows to use the reactor with almost any standard fluorimeter. Details of the construction are presented. Fluorescence spectra of Fmoc-group, both in solution and on the solid support, are given; effects of concentration quenching of the fluorescence are studied.


Two microphones spectral-coherence based speech enhancement for hearing aids using smartphone as an assistive device.
In this paper, we present a new Speech Enhancement (SE) technique capable of running on a smartphone, as an assistive device for hearing aids (HAs). The developed method incorporates the coherence between the speech and noise signals to obtain a SE gain function which is used in conjunction with the gain function obtained by Spectral Subtraction using adaptive gain averaging. SE using coherence based gain function is found to suppress the background noise well, while inducing speech distortion. On the other hand, SE using Spectral Subtraction improves speech quality with tolerable speech distortion, but introduces background musical noise for certain noise types. The weighted fusion of the two gain functions strikes a balance between noise suppression and speech distortion. Also it allows the user to control the weighting factor based on the noisy environment and their comfort level of hearing. The developed method is computationally fast and operates in real-time. The proposed method was evaluated for machinery, babble, and car noise types, using both objective and subjective measures for both quality and intelligibility of the enhanced speech. The results show significant improvements in comparison with stand-alone Spectral Subtraction with weighted gain averaging SE methods.


Stromal cell-derived factor-1 significantly induces proliferation, migration, and collagen type I expression in a human periodontal ligament stem cell subpopulation.
The pivotal role of chemokine stromal cell-derived factor-1 (SDF-1) in bone marrow mesenchymal stem cells recruitment and tissue regeneration has already been reported. However, its roles in human periodontal ligament stem cells (PDLSCs) remain unknown. PDLSCs are regarded as candidates for periodontal tissue regeneration and are used in stem cell-based periodontal tissue engineering. The expression of chemokine receptors on PDLSCs and the migration of these cells induced by chemokines and their subsequent function in tissue repair may be a crucial procedure for periodontal tissue regeneration. PDL tissues were obtained from clinically healthy premolars extracted for orthodontic reasons and used to isolate single-cell colonies by the limited-dilution method. Immunocytochemical staining was used to detect the expression of the mesenchymal stem cell marker STRO-1. Differentiation potentials were assessed by alizarin-red staining and oil-red O staining. The expression of SDF-1 receptor CXCR4 was evaluated by real-time polymerase chain reaction (PCR) and immunocytochemical staining. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and bromodeoxyuridine incorporation assay were used to determine the viability and proliferation of the PDLSC subpopulation. Expression of collagen type I and alkaline phosphatase was detected by real-time PCR to determine the effect of SDF-1 on cells differentiation. Twenty percent of PDL single-cell colonies expressed STRO-1 positively, and this specific subpopulation was positive for CXCR4 and formed minerals and lipid vacuoles after 4 weeks induction. SDF-1 significantly increased proliferation and stimulated the migration of this PDLSC subpopulation at concentrations between 100 and 400 ng/mL. CXCR4 neutralizing antibody could block cell proliferation and migration, suggesting that SDF-1 exerted its effects on cells through CXCR4. SDF-1 promoted collagen type I level significantly but had little effect on alkaline phosphatase level. SDF-1 may have the potential of promoting periodontal tissue regeneration by the mechanism of guiding PDLSCs to destructive periodontal tissue, promoting their activation and proliferation and influencing the differentiation of these stem cells.


Effects of a competitive antagonist of bradykinin on blood pressure and renal blood flow in anesthetized rats.
To examine a possible role of endogenous bradykinin in the regulation of blood pressure (BP) and renal blood flow (RBF), a newly synthesized competitive antagonist of bradykinin (B4147) was studied in anesthetized rats. Also, the question of whether the hypotensive effect of the converting enzyme inhibitor, captopril, is mediated partly by an accumulation of endogenous bradykinin was considered. The intravenous infusion of B4147 (25 micrograms/min) inhibited the depressor effect of exogenous bradykinin (0.5 microgram, i.v.) by 69%. After an intravenous injection of B4147 at doses of 25, 50 and 100 micrograms, BP increased and RBF decreased in a dose-dependent fashion. The increase in BP was not blocked by pretreatment with an angiotensin II antagonist (1-Sar-8-Ile angiotensin II; 20 micrograms/kg per min) or an alpha 1-blocker (prazosin; 0.1 mg/kg). The administration of captopril (1 mg/kg) decreased mean BP from 110 +/- 3.5 to 71 +/- 1.9 mmHg (P less than 0.001). However, the injection of B4147 (50 micrograms) after the administration of captopril elicited an increase in BP of 43% of the initial decrease induced by captopril. These results suggest that the effects of B4147 on BP and RBF are not mediated through angiotensin II or sympathetic alpha 1-stimulation. Endogenous bradykinin could contribute to the maintenance of BP and RBF in anesthetized rats, probably counter-balancing the vasoconstrictor mechanisms. It is also suggested that bradykinin may partly participate in the acute hypotensive effect induced by the converting enzyme inhibitor captopril.


The role of follicular T helper cells in patients with malignant lymphoid disease.
To investigate the dynamic change of follicular T helper cells (TFH) in patients with malignant lymphoid disease (MLD) and to explore its clinical significance. The dynamic change of TFH cells, ICOS+- and PD-1+ TFH cells at pretreatment and different treatment periods was determined by flow cytometry in 85 MLD patients. Concentration of interleukin 21 (IL-21) was evaluated by ELISA, and the correlation between clinical prognosis and the ratio of TFH cells was analyzed. Significantly increased ICOS+- and PD-1+ TFH cells were found in MLD patients at pretreatment compared to healthy controls. Decreased or even close to normal levels of ICOS+- and PD-1+ TFH cells were found at the end of treatment. However, in the patients with progressive disease, high levels of ICOS+- and PD-1+ TFH cells were found. Moreover, a significantly increased plasma IL-21 level was found in MLD patients. Negative correlation was found between the level of ICOS+-, PD-1+ TFH cells, as well as IL-21 and the prognosis of MLD. Significantly increased TFH cell ratios were found in patients with MLD, and decreased TFH cells ratios could be expected in those treatment-effective patients, which could be used as the therapeutic efficacy index.


The influence of membrane ion-permselectivity on electrokinetic concentration enrichment in membrane-based preconcentration units.
The performance of nanoporous hydrogel microplugs with varying surface charge density is described in concentrating charged analytes electrokinetically in a microfluidic device. A neutral hydrogel plug with a mean pore size smaller than the size of charged analytes acts as a simple size-exclusion membrane. The presence of fixed charges on the backbone of a nanoporous hydrogel creates ion-permselectivity which results in charge-selective transport through the hydrogel. This leads to the development of concentration polarization (CP) in the adjoining bulk electrolyte solutions under the influence of an applied electrical field. CP strongly affects the distribution of the local electrical field strength, in particular, in the vicinity of the hydrogel plug which can significantly reduce the concentration enrichment factors compared to the neutral hydrogel. A theoretical model and simulations are presented, together with experimental data, to explain the interplay of hydrogel or membrane cation-selectivity, electrical field-induced CP, and the distribution of the local electrical field strength with respect to concentration enrichment of negatively charged analytes at the cathodic membrane-solution interface.


Multiomics Reveals the Regulatory Mechanisms of Arabidopsis Tissues under Heat Stress.
Understanding the mechanisms of responses to high temperatures in Arabidopsis will provide insights into how plants may mitigate heat stress under global climate change. And exploring the interconnections of different modification levels in heat stress response could help us to understand the molecular mechanism of heat stress response in Arabidopsis more comprehensively and precisely. In this paper, we combined multiomics analyses to explore the common heat stress-responsive genes and specific heat-responsive metabolic pathways in Arabidopsis leaf, seedling, and seed tissues. We found that genes such as AT1G54050 play a role in promoting proper protein folding in response to HS (Heat stress). In addition, it was revealed that the binding profile of A1B is altered under elevated temperature conditions. Finally, we also show that two microRNAs, ath-mir156h and ath-mir166b-5p, may be core regulatory molecules in HS. Also elucidated that under HS, plants can regulate specific regulatory mechanisms, such as oxygen levels, by altering the degree of CHH methylation.


Being ready to treat Ebola virus disease patients.
As the outbreak of Ebola virus disease (EVD) in West Africa continues, clinical preparedness is needed in countries at risk for EVD (e.g., United States) and more fully equipped and supported clinical teams in those countries with epidemic spread of EVD in Africa. Clinical staff must approach the patient with a very deliberate focus on providing effective care while assuring personal safety. To do this, both individual health care providers and health systems must improve EVD care. Although formal guidance toward these goals exists from the World Health Organization, Medecin Sans Frontières, the Centers for Disease Control and Prevention, and other groups, some of the most critical lessons come from personal experience. In this narrative, clinicians deployed by the World Health Organization into a wide range of clinical settings in West Africa distill key, practical considerations for working safely and effectively with patients with EVD.


Imaging cerebral microbleeds in Cushing's disease evaluated by quantitative susceptibility mapping: an observational cross-sectional study.
Cushing's disease (CD) is a rare clinical syndrome characterized by chronic exposure to hypercortisolism due to an adrenocorticotropic hormone-secreting pituitary adenoma. The adverse effects of chronic exposure to hypercortisolism on the human brain remain unclear. The purpose of this study was to assess the prevalence of cerebral microbleeds (CMBs) in CD patients and their associations with clinical characteristics. In this study, 48 active CD patients, 39 remitted CD patients, and 52 healthy control (HC) subjects underwent MRI. CD patients also underwent neuropsychological testing and clinical examinations. The number, locations, and volumes of CMBs were assessed on quantitative susceptibility mapping (QSM) images and with the Microbleed Anatomical Rating Scale. The correlation between CMBs and clinical characteristics was explored. The prevalence of CMBs among active and remitted CD patients was higher than that among HCs (16.3%, 20.5%, and 3.3%, respectively). Moreover, the age of CD patients with CMBs were much younger than HCs with CMBs. Furthermore, the increased number of CMBs in active CD patients was associated with increased cerebrospinal fluid (CSF) volumes in remitted CD patients. Chronic exposure to hypercortisolism may be relevant to CMBs and significantly correlated with altered brain volumes in CD.


The BARI 2D study: a randomised trial of therapies for type 2 diabetes and coronary artery disease.
The Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial randomized 2368 patients with type 2 diabetes (T2DM) and coronary artery disease to either prompt revascularization or intensive medical therapy alone; and to either insulin-sensitization or insulin-provision diabetes therapy. Randomization was stratified by proposed revascularization method. Five-year survival and major cardiovascular events (MACE) were similar in study subgroups except in the coronary bypass surgery (CABG) stratum where there were fewer MACE after revascularization. There was less hypoglycaemia and weight gain, and greater apparent benefit from CABG in the insulin sensitization group. BARI 2D has provided important data for clinicians.


Differentiation of primary central nervous system lymphoma from glioblastoma using optical coherence tomography based on attention ResNet.
Significance: Differentiation of primary central nervous system lymphoma from glioblastoma is clinically crucial to minimize the risk of treatments, but current imaging modalities often misclassify glioblastoma and lymphoma. Therefore, there is a need for methods to achieve high differentiation power intraoperatively. Aim: The aim is to develop and corroborate a method of classifying normal brain tissue, glioblastoma, and lymphoma using optical coherence tomography with deep learning algorithm in an ex vivo experimental design. Approach: We collected tumor specimens from ordinal surgical operations and measured them with optical coherence tomography. An attention ResNet deep learning model was utilized to differentiate glioblastoma and lymphoma from normal brain tissues. Results: Our model demonstrated a robust classification power of detecting tumoral tissues from normal tissues and moderate discrimination between lymphoma and glioblastoma. Moreover, our results showed good consistency with the previous histological findings in the pathological manifestation of lymphoma, and this could be important from the aspect of future clinical practice. Conclusion: We proposed and demonstrated a quantitative approach to distinguish different brain tumor types. Using our method, both neoplasms can be identified and classified with high accuracy. Hopefully, the proposed method can finally assist surgeons with decision-making intraoperatively.


Dietary Lycopene Supplementation Improves Cognitive Performances in Tau Transgenic Mice Expressing P301L Mutation via Inhibiting Oxidative Stress and Tau Hyperphosphorylation.
Oxidative stress is implicated in the pathogenesis of Alzheimer's disease (AD) and other tauopathies and participates in their development by promoting hyperphosphorylation of microtubule-associated protein tau. Lycopene, as an effective antioxidant, combined with vitamin E seemed to be additive against oxidative stress. The present study was undertaken to examine whether lycopene or lycopene/vitamin E could exert protective effects on memory deficit and oxidative stress in tau transgenic mice expressing P301L mutation. P301L transgenic mice were assigned to three groups: P301L group (P301L), P301L+lycopene (Lyc), and P301L+lycopene/vitamin E (Lyc+VE). Age-matched C57BL/6J mice as wild type controls (Con) were used in the present study. Spatial memory was assessed by radial arm while passive memories were evaluated by step-down and step-through tests. Levels of tau phosphorylation were detected by western blot. Oxidative stress biomarkers were measured in the serum using biochemical assay kits. Compared with the control group, P301L mice displayed significant spatial and passive memory impairments, elevated malondialdehyde (MDA) levels and decreased glutathione peroxidase (GSH-Px) activities in serum, and increased tau phosphorylation at Thr231/Ser235, Ser262, and Ser396 in brain. Supplementations of lycopene or lycopene/vitamin E could significantly ameliorate the memory deficits, observably decreased MDA concentrations and increased GSH-Px activities, and markedly attenuated tau hyperphosphorylation at multiple AD-related sites. Our findings indicated that the combination of lycopene and vitamin E antioxidants acted in a synergistic fashion to bring significant effects against oxidative stress in tauopathies.